In recent years there has been a strong interest in the potential effect of migraine disease on other illnesses. Our understanding of the complex pathophysiology of migraine disease that may underlie nonheadache symptoms and syndromes is currently marked by a long list of comorbid disorders. The connection of migraine to other conditions is at various levels of explanation, ranging from some intriguing clinical observations to accepted criteria as a migraine subtype. This is a snapshot of the level of current knowledge of migraine comorbidities and the significance of this information, but the complexity of this subject will be a challenge for a generation of clinicians and scientists.

Some children have visual disturbances that occur in the absence of, or are out of proportion to, their objective ophthalmological findings. These symptoms reflect a wide range of processes that may be benign or a sign of neurological, systemic, or psychiatric disease. This chapter deals with the neuro-ophthalmologic detection of organic and psychogenic disorders that may manifest as transient or unexplained visual loss, along with other episodic visual disturbances that occur in childhood. In these cases, several formidable problems confront the physician who is trying to reach the correct diagnosis. The descriptions of episodic visual disturbances and hallucinations in children are generally less complex in detail than those in the adult population because children have a limited vocabulary and a limited experiential basis of sensory phenomena to draw upon.

Chronic migraine is a debilitating primary headache disorder associated with high personal, familial, and social impact. The diagnosis is made when there are at least 15 headache days monthly including 8 migraine days per month for at least 3 months. The prevalence is 1.4–2.2% in the population. Among individuals diagnosed with chronic migraine, there may be significant variability in headache days with a potential to remit, remain unchanged, or progress to even greater disability. Most chronic migraine progresses from episodic migraine, with several identified risk factors for chronic migraine and migraine progression. The exact mechanism of chronic migraine is unknown but is associated with an increased cortical excitability, central sensitization, alternations in nociceptive signaling, as well as physiological, structural, and functional brain changes. There is evidence for both nonpharmacological and pharmacological treatment options to restore function. The best currently established pharmacologic evidence for the treatment of chronic migraine is onabotulinumtoxinA and topiramate. Behavioral treatments may improve headache symptoms and comorbidities. Emerging data shows potential benefit for neurostimulation, and large well-designed studies are needed. Multicenter randomized placebo-controlled studies of monoclonal antibodies to the calcitonin gene-related peptide, or its receptor, have demonstrated efficacy, tolerability, and safety. Biomarkers are needed to guide prognosis, treatment response, and clinical trials. The concept and management of refractory chronic migraine is discussed, and clinically meaningful endpoints are reviewed.

Migraine is a recurrent clinical syndrome characterised by combinations of neurological, gastrointestinal and autonomic manifestations. The exact patho-physiological disturbances that occur with migraine have yet to be elucidated; however, cervico-trigemino-vascular dysfunctions appear to be the primary cause.

Despite advances in the understanding of the pathophysiology of migraine and new effective treatment options, migraine remains an under-diagnosed, under-treated and poorly treated health condition. Most patients will unsuccessfully attempt to treat their headaches with over-the-counter medications.

Few well designed, placebo-controlled studies are available to guide physicians in medication selection. Recently published evidence-based guidelines advocate migraine-specific drugs, such as serotonin 5-HT1b/1d agonists (the ‘triptans’) and dihydroergotamine mesylate, for patients experiencing moderate to severe migraine attacks. Additional headache attack therapy options include other ergotamine derivatives, phenothiazines, nonsteroidal anti-inflammatory agents and opioids.

Purpose of review

Migraine causes more years of life lived with disability than almost any other condition in the world and can significantly impact the lives of individuals with migraine, their families, and society. The use of medication for the prevention of migraine is an integral component to reducing disability caused by migraine. There are many different drug classes that have been investigated and shown efficacy in migraine prophylaxis. This article examines several of the classes of medications that are used for migraine preventive treatment, specifically, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, serotonin antagonists, alpha-adrenergic agonists, and N-methyl-d-aspartic acid receptor antagonists.

Recent findings

There have been randomized control trials investigating medications in these drug classes since the most recent guidelines for migraine prevention in adults were published by the American Academy of Neurology, American Headache Society, and the Canadian Headache Society. In these investigations, enalapril, candesartan, and memantine all demonstrated efficacy for migraine prevention. The evidence for these and the aforementioned drug classes are reviewed.

Summary

When oral medications are being selected for migraine prevention, comorbid and coexistent medical conditions, concomitant medications, patient preference, and pregnancy and breast-feeding plans should be considered. Within the drug classes discussed, memantine and candesartan have a moderate level of evidence for efficacy.

Migraine is prevalent in children and adolescents and constitutes an important cause of disability in this population. Early, effective treatment of paediatric migraine is likely to result in improved outcomes. Findings from the past few years suggest that a biopsychosocial approach that uses interdisciplinary multimodal care is most effective for treatment of migraine in the paediatric population. Key elements of this management include effective and timely acute pharmacological interventions (such as NSAIDs and/or triptans), education of patients regarding self-management techniques, and psychological interventions such as biofeedback, relaxation and cognitive–behavioural therapy. The efficacy of current pharmacological or nutraceutical interventions for migraine prevention in children and adolescents is unclear, although reported placebo response patterns suggest that the effect of pill-taking behaviour is positive. As such, clinicians can consider adding a preventive intervention that involves a daily pill-taking behaviour to evidence-based non-pharmacological first-line preventive interventions (such as cognitive–behavioural therapy). More rigorous research is needed to delineate the role of pharmacological and nutraceutical interventions, the mechanisms of the clinically relevant placebo response, and interventions that enhance this response for migraine prevention in this population. Given the prevalence of migraine, cost-effective and efficacious strategies are needed for the large-scale delivery of interdisciplinary multimodal paediatric migraine care.

Some children have visual disturbances that occur in the absence of, or are out of proportion to, their objective ophthalmological findings. These symptoms reflect a wide range of processes that may be benign or a sign of neurological, systemic, or psychiatric disease. This chapter deals with the neuro-ophthalmologic detection of organic and psychogenic disorders that may manifest as transient or unexplained visual loss of the same episodic visual disturbances that occur in childhood, but several formidable problems confront the physician who is trying to reach the correct diagnosis. The descriptions of episodic visual disturbances and hallucinations in children are less complex in detail than those of the adult population because children have limited vocabulary and limited experiential basis of sensory phenomenon to draw upon.

Migraine aura consists of fully reversible focal neurologic symptoms that may precede or coexist with headache in a significant minority of migraine patients. Typical aura symptoms include visual, sensory, and language disturbances. The most recent International Classification of Headache Disorders, 3rd edition (beta version) has added other aura types such as brainstem localizing symptoms, lateralizing weakness, and monocular visual loss. Currently available data from animal models and functional neuroimaging in humans implicate cortical spreading depression (CSD) as the phenomenon underlying migraine aura. Ongoing study suggests that susceptibility to migraine aura and CSD may be genetically mediated. CSD appears to be a potential target for future development of migraine-specific preventive therapies.

Many women experience headaches, including migraine, in association with their menstrual cycles. Although definitions vary, menstrual migraine generally refers to migraine without aura that occurs within several days prior to and several days after the onset of menses.

Although menstrual migraine has been reported to be more difficult to treat than other types of migraines, there is no evidence from controlled clinical trials to support this assertion. Thus, the pharmacological treatment of menstrual migraine should be similar to that of other types of migraines, except with respect to the use of hormonal manipulations to treat menstrual migraine.

Serotonin 5-HT1B/1D receptor agonists (triptans) are effective for the acute treatment of both menstrual and non-menstrual migraines. When used as acute therapy, a triptan should be administered early, when the headache is still mild in severity. Ideally, an acute therapy will provide rapid and complete pain relief with no disability. Some patients may require preventive therapy for menstrual migraine based on suboptimal response to an adequate trial of acute therapy. Patient diaries that record headache onset, relationship to the menstrual cycle and treatment response through three complete cycles will allow accurate prediction of the onset of menstrual migraine; this information is also needed to make decisions about timing of intermittent preventive therapy. The goals of intermittent preventive therapy are to reduce the frequency, duration and intensity of menstrual migraine attacks.

Clinical studies show that triptans are effective when used as either acute therapy or as intermittent preventive therapy for menstrual migraine. Sumatriptan and zolmitriptan have been evaluated in prospective, randomised, controlled trials for acute treatment. Retrospective analyses and open-label studies also support the use of other triptans as acute therapy. In addition, sumatriptan, frovatriptan, naratriptan and zolmitriptan have been evaluated as intermittent preventive therapy in prospective studies. Thus, data from clinical studies indicate that triptans are effective for the treatment of menstrual migraine.

Vestibular migraine is a clinical syndrome of the central nervous system that is characterized by episodic vestibular symptoms and a history of migraines. It affects approximately 1% of the population [1] and is one of the most common diagnoses in children presenting with vertigo [2].